The broad objective of this project is to reach a better understanding of the mechanisms underlying "neurotrophic" control of mammalian skeletal muscles. To accomplish this aim we have studied the effects of a soluble protein nerve extract from rat obturator nerve on the activity of 16S acetylcholinesterase (AChE) from anterior gracilis muscles maintained in organ culture. The gracilis muscles, in vivo, the 16S form of AChE is exclusively found in the motor endplates (1) where its activity drastically decreases with denervation; the time of onset of such decrease being directly related to the length of nerve stump that remains attached to the muscle (2). A similar decay of 16S AChE is also observed in gracilis muscles maintained in organ culture for up to 5 days. Addition of nerve extract to the nutrient media partly prevented the 16S AChE decrease, whereas rat serum had no effect. Further, we found that the nerve extract did not contain 16S AChE, nor did serum or the nutrient media, and that the extract also decreased the amount of total AChE activity released by the muscle. So far, our results suggest that "trophic" regulation of endplate 16S AChE is mediated by a soluble substance(s) present in the motor nerve and supplied to the muscle. In turn, such substance(s) might be conveyed by axonal transport inasmuch as this process is also essential for maintenance of AChE at the endplates (3). Future experiments consider further characterization of the effects of nerve extracts as to their physiological significance and specificity and isolation of the active components.